Combination of tonic and burst stimulations to treat neurological disorders

ABSTRACT

The present application relates to a new stimulation design which can be utilized to treat neurological conditions. The stimulation system produces a combination of burst and tonic stimulation which alters the neuronal activity of the predetermined site, thereby treating the neurological condition or disorder.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/109,098, filed Apr. 24, 2008, now U.S. Pat. No. 8,364,273, whichclaims the benefit of U.S. Provisional Application No. 60/913,613, filedApr. 24, 2007, the disclosures of which are fully incorporated herein byreference for all purposes.

BACKGROUND

The present application relates to a stimulation system and method thatutilizes combined burst and tonic stimulation parameters to treatneurological conditions and/or disorders.

Different firing modes or frequencies occur in the brain and/or otherneuronal tissue, for example tonic firing and burst firing (irregular orregular burst firing). Such firing modes can be utilized for normalprocessing of information, however, alteration of the firing modes, mayalso lead to pathology.

For example, certain neurological conditions are associated withhyperactivity of the brain and can be traced to a rhythmic burst firingor high frequency tonic firing (e.g., tinnitus, pain, and epilepsy).Other conditions can be associated with an arrhythmic burst firing or adesynchronized form of tonic and burst firing (e.g., movement disordersand hallucinations).

During the past decade, neuromodulation systems have been used tomodulate various areas of the brain, spinal cord, or peripheral nerves(See, for example, U.S. Pat. Nos. 6,671,555; 6,690,974). These types ofsystems utilize tonic forms of electrical stimulation. Recently bursttranscranial magnetic stimulation (TMS) at theta frequencies has beendeveloped (Huang et al., 2005). Theta burst TMS has been shown toproduce an effect on motor and visual cortex by suppressing excitatorycircuits after a short application period of only 20-190 s (Huang etal., 2005; Di Lazzaro et al., 2005; Franca et al., 2006). However, thereis not a system that utilizes both types of electrical stimulation.

Thus, the inventor is the first to describe a neuromodulation design orstimulation parameters in which the stimulation parameters produce acombination of burst stimulation and tonic stimulation to override oralter the pathological and/or physiological stimulation to treat aneurological condition.

SUMMARY

In one representative embodiment, a method of neurostimulation comprisesgenerating, by an implantable pulse generator, a stimulus that is aburst stimulus that comprises a plurality of groups of spike pulses incombination with one or more single spike pulses; providing the burststimulus from the implantable pulse generator to a medical lead; andapplying the burst stimulus to nerve tissue of the patient via one orseveral electrodes of the medical lead.

In further embodiments, a tonic stimulus is delivered within theinter-burst interval, for example, the tonic spike stimulus may be fixedin relation to the preceding burst stimulus or the subsequent burststimulus. Yet further, the timing of the burst stimulus may be fixed inrelation to the preceding tonic spike stimulus or subsequent the tonicspike stimulus.

The foregoing has outlined rather broadly certain features and/ortechnical advantages in order that the detailed description that followsmay be better understood. Additional features and/or advantages will bedescribed hereinafter which form the subject of the claims. It should beappreciated by those skilled in the art that the conception and specificembodiment disclosed may be readily utilized as a basis for modifying ordesigning other structures for carrying out the same purposes. It shouldalso be realized by those skilled in the art that such equivalentconstructions do not depart from the spirit and scope of the appendedclaims. The novel features, both as to organization and method ofoperation, together with further objects and advantages will be betterunderstood from the following description when considered in connectionwith the accompanying figures. It is to be expressly understood,however, that each of the figures is provided for the purpose ofillustration and description only and is not intended as a definition ofthe limits of the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of the present application, referenceis now made to the following descriptions taken in conjunction with theaccompanying drawing, in which:

FIGS. 1A-1B illustrate exemplary combinations of burst and tonicstimuli. FIG. 1A shows the tonic stimulation surrounding the burststimulation. FIG. 1B shows tonic and burst stimulation can be combinedon the same poles or center tone.

FIG. 2 illustrate an exemplary burst stimulus having ramping.

FIG. 3 is a block diagram of steps according to a method for treating aneurological disorder using a stimulation system.

FIGS. 4A-4B illustrate an example stimulation system for electricallystimulating neuronal tissue.

FIGS. 5A-5I illustrate example electrical stimulation leads that may beused to electrically stimulate neuronal tissue.

FIG. 6 depicts an implantable pulse generator that may be programmed togenerate burst and tonic stimulation according to one representativeembodiment.

FIG. 7 depicts stimulation parameters for a number of pulses of burstand tonic stimulation according to one representative embodiment.

FIG. 8 depicts a stimulation program for defining burst and tonicstimulation according to one representative embodiment.

DETAILED DESCRIPTION I. Definitions

Unless defined otherwise, technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art. For purposes of the present application, the following termsare defined below.

As used herein, the use of the word “a” or “an” when used in conjunctionwith the term “comprising” in the claims and/or the specification maymean “one,” but it is also consistent with the meaning of “one or more,”“at least one,” and “one or more than one.” Still further, the terms“having”, “including”, “containing” and “comprising” are interchangeableand one of skill in the art is cognizant that these terms are open endedterms.

As used herein, the term “in communication” refers to the stimulationlead being adjacent, in the general vicinity, in close proximity, ordirectly next to or directly on the predetermined stimulation site.Thus, one of skill in the art understands that the lead is “incommunication” with the predetermined site if the stimulation results ina modulation of neuronal activity. The predetermined site may beselected from the group consisting of the peripheral neuronal tissue orcentral neuronal tissue. Central neuronal tissue includes, but is notlimited to brain tissue, brainstem, spinal tissue.

As used herein, the use of the term “dorsal column” refers to conductingpathways in the spinal cord that are located in the dorsal portion ofthe spinal cord between the posterior horns, and which comprisesafferent somatosensory neurons. The dorsal column is also known as theposterior funiculus.

As used herein, the use of the words “epidural space” or “spinalepidural space” is known to one with skill in the art, and refers to anarea in the interval between the dural sheath and the wall of the spinalcanal.

As used herein the term “modulate” refers to the ability to regulatepositively or negatively neuronal activity. Thus, the term modulate canbe used to refer to an increase, decrease, masking, altering, overridingor restoring of neuronal activity.

As used herein, the terms “spike”, “action potential”, and “pulse”, allrefer to a rapid rise and fall of voltage or current. One skilled in theart realizes that the term action potential generally refers to a spikeor pulse that is produced by neurons. One skilled in the art alsorecognizes that the term action potential can also be expanded toinclude the spiking of cells in other excitable tissues. The terms spikeand pulse may refer to action potentials produced by neurons or otherexcitable cells. Alternatively, the terms spike and pulse may refer tovoltage or current generated by a pulse generator device. Those of skillin the art are aware that the spikes generated by a pulse generatordevice can be either bipolar or monopolar or a combination of bothbipolar and monopolar. The terms “inter-spike interval” or “inter-pulseinterval” refer to the period of time between two action potentials,spikes, or pulses. However, one of skill in the art also realizes thatnaturally occurring spikes do not necessarily occur at a fixed rate;this rate can be variable. In such cases an average inter-spike intervalmay be used to define the average period of time between two actionpotentials.

As used herein, the term “tonic” as well as the phrases “tonic firing”,“tonic spike”, “tonic pulse”, or “tonic mode” refers to any process inwhich individual spikes occur with relatively long inter-spikeintervals. Tonic firing modes may be defined operatively as havingspikes that occur with sufficiently long interspike intervals thatsignificant temporal summation of cellular depolarizations does notoccur.

As used herein, the term “burst” as well as the phrases “burst firing”,“burst spikes”, or “burst mode” refers to a rapid succession of two ormore neuronal action potentials in the approximate frequency range of(100-1000 Hz) (Beurrier et al., 1999). Similarly, a burst spike may bedescribed as a spike that is preceded or followed by another spikewithin a short time interval of approximately (0.5 psec-10 msec)(Matveev, 2000). Those skilled in the art recognize that a burst canrefer to a plurality of groups of spike pulses. A burst is a train ofaction potentials that, possibly, occurs during a ‘plateau’ or ‘activephase’, followed by a period of relative quiescence called the ‘silentphase’ (Nunemaker, Cellscience Reviews Vol 2 No. 1, 2005.) A burst maybe operatively defined as a period in time in which two or more spikesoccur relatively rapidly, such that the spikes summate in a non-linearfashion. The period of time between the beginning of a burst and the endof the same said burst is defined as the “intra-burst interval”. Theperiod of time between two bursts is known as the “inter-burstinterval”. The inter-burst interval may not be affected by the presenceof any number of tonic spikes located anywhere within a series of two ormore bursts. One skilled in the art is also aware that burst firing canalso be referred to as phasic firing, rhythmic firing (Lee 2001), pulsetrain firing, oscillatory firing and spike train firing, all of theseterms used herein are interchangeable.

As used herein, “burst stimulation” refers to pulses generated by apulse generator that is similar to burst firing of action potentialswithin neural tissue. Specifically, burst stimulation includes multiplediscrete bursts with each burst comprising multiple pulses or spikes.Burst stimulation may occur from a plateau or elevated pulse amplitudeapplied by the pulse generator. Also, a hyper-polarizing or otherpre-conditioning pulse may precede the burst. A charge balancing pulseor pulses may be applied within the burst or at the end of the burst.Within a burst of electrical pulses, the electrical pulses are separatedfrom each adjacent pulse by an inter-pulse interval. The intra-burstinter-pulse interval can be about 0.5 microseconds to about 10milliseconds. However, one of skill in the art also realizes that theintra-burst spike rate does not necessarily occur at a fixed rate; thisrate can be variable.

As used herein, the term “neuronal” refers to a cell which is amorphologic and functional unit of the brain, brainstem, spinal cord,and peripheral nerves.

As used herein, the term “peripheral neuronal tissue” refers to anyneuronal tissue associated with a nerve root, root ganglion, orperipheral nerve that is outside the brain and the spinal cord.Peripheral neuronal tissue also includes cranial nerves. It includes theautonomous nervous system, inclusive of (ortho-)sympathetic andparasympathetic system. Furthermore, those of skill in the art realizethat peripheral neuronal tissue also includes stimulating the peripheralnervous tissue associated with a dermatome.

As used herein, the term “dermatome” refers to the area of skininnervated by a single dorsal root. One of skill in the art realizesthat the boundaries of dermatomes are not distinct and in fact overlapbecause of overlapping innervations by adjacent dorsal roots. Dermatomesare divided into sacral (S), lumbar (L), thoracic (T) and cervical (C).Yet further, as used herein, the term “dermatome” includes all theneuronal tissues located within the region or adjacent to the dermatomearea, for example, it may include any peripheral nerve, or any cervicalnerve root (e.g., C1, C2, C3, C4, C5, C6, C7 and C8) that may innervatethe dermatome. For example, the C2/C3 dermatome area may comprise anyperipheral nerve (e.g., the occipital nerve (the greater, the lesser,the third and the suboccipital nerve), the great auricular nerve, thetransverse cervical nerve, the supraclavicular nerve, spinal accessorynerve, phrenic nerve, dorsal scapular nerve) that arises from the C2 orC3 nerve root.

As used herein, the term “central neuronal tissue” refers to neuronaltissue associated with the brain, spinal cord or brainstem.

As used herein, the term “neurology” or “neurological” refers toconditions, disorders, and/or diseases that are associated with thenervous system. The nervous system comprises two components, the centralnervous system, which is composed of the brain and the spinal cord, andthe peripheral nervous system, which is composed of ganglia and theperipheral nerves that lie outside the brain and the spinal cord. One ofskill in the art realizes that the nervous system may be linguisticallyseparated and categorized, but functionally the system is interconnectedand interactive. Yet further, the peripheral nervous system is dividedinto the autonomic system (parasympathetic and sympathetic), the somaticsystem and the enteric system. Thus, any condition, disorder and/ordisease that effect any component or aspect of the nervous system(either central or peripheral) are referred to as a neurologicalcondition, disorder and/or disease. As used herein, the term“neurological” or “neurology” encompasses the terms “neuropsychiatric”or “neuropsychiatry” and “neuropsychological” or “neuropsychology”.Thus, a neurological disease, condition, or disorder includes, but isnot limited to tinnitus, epilepsy, depression, anxiety, Parkinson'sDisease, autonomic dysfunctions, etc.

As used herein, the term “neuropsychiatry” or “neuropsychiatric” refersto conditions, disorders and/or diseases that relate to both organic andpsychic disorders of the nervous system.

As used herein, the term “neuropsychological” or “neuropsychologic” orneuropsychology refers to conditions, disorders and/or disease thatrelate to the functioning of the brain and the cognitive processors orbehavior.

As used herein, “spinal cord,” “spinal nervous tissue associated with avertebral segment,” “nervous tissue associated with a vertebral segment”or “spinal cord associated with a vertebral segment or level” includesany spinal nervous tissue associated with a vertebral level or segment.Those of skill in the art are aware that the spinal cord and tissueassociated therewith are associated with cervical, thoracic, and lumbarvertebrae. As used herein, C1 refers to cervical vertebral segment 1, C2refers to cervical vertebral segment 2, and so on. T1 refers to thoracicvertebral segment 1, T2 refers to thoracic vertebral segment 2, and soon. L1 refers to lumbar vertebral segment 1, L2 refers to lumbarvertebral segment 2, and so on, unless otherwise specifically noted. Incertain cases, spinal cord nerve roots leave the bony spine at avertebral level different from the vertebral segment with which the rootis associated. For example, the T11 nerve root leaves the spinal cordmyelum at an area located behind vertebral body T8-T9 but leaves thebony spine between T11 and T12.

As used herein, the term “stimulate” or “stimulation” refers toelectrical, chemical, magnetic, thermal and/or other such stimulationthat modulates the predetermined neuronal sites.

As used herein, the term “treating” and “treatment” refers to modulatingpredetermined neuronal sites (central neuronal tissue and/or peripheralneuronal tissue) so that the subject has an improvement in the diseaseor condition, for example, beneficial or desired clinical results. Forpurposes of this application, beneficial or desired clinical resultsinclude, but are not limited to, alleviation of symptoms, diminishmentof extent of disease, stabilized (e.g., not worsening) state of disease,delay or slowing of disease progression, amelioration or palliation ofthe disease state, and remission (whether partial or total), whetherdetectable or undetectable. One of skill in the art realizes that atreatment may improve the disease condition, but may not be a completecure for the disease.

II. Clinical Relevance

A. Tinnitus

Introduction

Tinnitus is an auditory phantom percept (Jastreboff, 1990; Muhlnickel etal., 1998) related to reorganization (Muhlnickel et al., 1998) andhyperactivity (Eggermont and Roberts, 2004) of the auditory system. Theauditory system consists of two main parallel pathways supplyingauditory information to the cerebral cortex: the topographicallyorganized lemniscal (classical) system, and the non-topographicextralemniscal (non-classical) system. The classical pathways use theventral thalamus, the neurons of which project to the primary auditorycortex whereas the non-classical pathways use the medial and dorsalthalamic nuclei that project to the secondary auditory cortex andassociation cortices, thus bypassing the primary cortex (Møller, 2003).While neurons in the classical pathways only respond to one modality ofsensory stimulation, many neurons in the non-classical pathway respondto more than one modality. Neurons in the ventral thalamus fire in atonic or semi-tonic mode while neurons in the medial and dorsal thalamusfire in bursts (He and Hu, 2002; Hu et al., 1994). The non-classicalpathways receive their input from the classical pathways, which meansthat the ascending auditory pathways are a complex system of at leasttwo main parallel systems that provide different kinds of processing andwhich interact with each other in a complex way. Both systems providesensory input to the amygdala through a long cortical route, and inaddition, the non-classical pathways provide subcortical connections tothe lateral nucleus of the amygdala from dorsal thalamic nuclei (LeDoux,1993).

Studies in humans have indicated that some patients with tinnitus havean abnormal activation of the non-classical auditory system (Moller etal., 1992). Studies of animal models of tinnitus have shown that burstfiring is increased in the non-classical system (Chen and Jastreboff,1995; Eggermont, 2003; Eggermont and Kenmochi, 1998) and tonic firingactivity is increased in the classical system Brozoski et al., 2002;Kaltenbach and Afman, 2000; Kaltenbach et al., 1998; Kaltenbach et al.,2004; Zacharek et al., 2002; Zhang and Kaltenbach, 1998). Interestingly,not only tonic firing but also burst firing is increased in neurons inthe primary auditory cortex in animal models of tinnitus (Ochi andEggermont, 1997). Studies in patients with intractable tinnitus haveshown that tonic electrical stimuli of the primary and secondaryauditory cortex can suppress pure tone tinnitus, but not whitenoise/narrow band noise tinnitus (De Ridder et al., 2006).

The inventors have tested the hypothesis that noise-like tinnitus may becaused by increased burst firing in the non-topographic (extralemniscal)system, whereas pure tone tinnitus may be the result of increased tonicfiring in the topographic (lemniscal) system. Transcranial magneticstimulation (TMS), a non-invasive tool, was shown to modulate theneuronal activity of the auditory cortex thereby modulating theperception of tinnitus (De Ridder et al., 2005; De Ridder et al., 2007a;Eichhammer et al., 2003; Kleinjung et al., 2005; Londero et al., 2006;Plewnia et al., 2003). It has been demonstrated that tonic stimulationcan suppress pure tone tinnitus, but not narrow band noise, whereasburst TMS can suppress narrow band or white noise tinnitus (noise-like)(De Ridder et al., 2007b; De Ridder et al., 2007a).

In the clinical setting, cases of tinnitus are commonly complex in thatthe patient suffers from more than one type (i.e. pure tone, narrowband, white noise) of tinnitus in one or both ears. As such, it isunlikely that tonic mode or burst mode alone will alleviate thesymptoms.

Methods and Materials

Four patients with both unilateral noise-like and pure tone (VR)tinnitus were implanted with electrodes for stimulation therapy usingboth tonic and burst stimulation parameters. In three patients, theelectrodes (Lamitorode 44 stimulation lead available from ANS Medical,Plano, Tex., USA) were implanted in the auditory cortex, and one patientwas implanted with a cervical dorsal column stimulation electrode(Lamitrode 44 stimulation lead). All patients underwent burststimulation at 6, 18, or 40 Hz consisting of 5 spikes with 1 ms pulsewidth, 1 ms interspike interval in a charged balanced manner and 6, 18,or 40 Hz tonic mode interspersed between or around the bursts (FIGS. 1Aand 1B). The stimuli were delivered by an 8 channel digitalneurostimulator (DS8000, World Precision Instruments, Hertfordshire,England/Sarasota, Fla., USA), capable of delivering tonic and burst modestimulation.

If the patients benefited from the stimulation, a commercially availableIPG capable of burst mode was implanted (EON® implantable pulsegenerator from ANS Medical, Plano, Tex., USA), programmed with similarsettings, using a custom made programmer. The only difference to thestimuli delivered with the external stimulator and the EON® implantablepulse generator, was the ramping used with the EON® implantable pulsegenerator (FIG. 2). The ramp was chosen to copy naturally occurringburst firing as closely as possible.

Results

The below Table 1 shows that by using a combination of tonic and burststimulation parameters patients suffering from pure tone and noise-liketinnitus can be treated. The tonic and burst stimulation can be combinedon the same poles or center tone (FIG. 1B) or surrounding the burststimulation with tonic stimulation (FIG. 1A).

TABLE 1 Intra-Burst Freq Spike Rate Suppression Patient Hz Burst TonicHz Spikes # of Tinnitus PB (DC) 6 Yes Yes 500 5 95% RM (AC) 40 Yes Yes500 5 100%  DA (AC) 40 Yes Yes 500 5 90% VR (AC) 18 Yes Yes 500 5 90%

CONCLUSION

Thus, in cases of complex tinnitus combinations of burst and tonic modestimulation were shown to effectively reduce the occurrence and severityof symptoms.

Although tonic mode stimulation alone is sufficient to reduce symptomoccurrence and severity in many simple cases of pure tone tinnitus, thesymptoms are rarely completely abolished. Moreover, in many cases wheresymptoms are reduced, the effect of tonic mode stimulation is relativelyshort lasting and repeated treatments result in significantly reducedefficacy over time. Stimulation protocols combining burst and tonic modestimulation are significantly more effective at reducing symptoms inpatients suffering from pure tone tinnitus, the effects of a singletreatment last longer, and there is no significant reduction in efficacywith repeated treatment. Yet further, the combination of burst and tonicstimulation is effective at reducing the symptoms or severity ofpatients that suffer from both pure tone tinnitus and noise-liketinnitus. Yet further, the combination of burst and tonic stimulationcan act as an anti-habituation protocol.

Clinical Application

In view of the above results for the combination of burst and tonicstimulation, one of skill in the art can realize that such stimulationprotocols can be used to treat neurological diseases/disorders havingboth a topographic (lemniscal system) and the non-topographic system(extralemniscal system) component. One such exemplary disease/disordermay include chronic pain. For example, typically, tonic stimulation isused to treat chronic pain. Tonic stimulation alters the topographic orlemniscal system resulting in the treatment of chronic pain. Thedownside to using tonic stimulation to treat chronic pain is thattypically the pain may be replaced with paresthesias, which acts throughthe non-topographic system. Thus, an alternative to treat chronic painwithout paresthesias may be to utilize a stimulation protocol thatemploys both burst and tonic stimulation, thereby altering both thenon-topographic and the topographic system to result in treatment ofchronic pain.

Yet further, another advantage of this type of combination protocol isthe ability of this combination of stimulation to reduce and/or preventanti-habituation or anti-adaptation of electrical stimulation. Those ofskill in the art are aware of the problem that occurs with continualelectrical stimulation in that the brain may adapt to the stimulationand the protocol is no longer effective to treat the symptoms. Thus, acombination protocol as described herein can alleviate this type ofadaptation and or habituation.

III. Detailed Discussion of the Procedure

The following section more generally describes FIG. 3 or an example of aprocedure for treatment using a combination of burst and tonicstimulation that optimizes the following four parameters; location forelectrode placement, a set and/or range of stimulation protocols thatcan most completely eliminate neurological disease/disorder, a setand/or range of stimulation protocols that requires the lowest voltage,and a protocol that maintains treatment efficacy over long periods oftime, for example, the protocol can prevent habituation. Also, theprotocol can be used to enhance a standard tonic and/or burst stimulusprotocol such that both the non-topographic and the topographic systemsare stimulated resulting in treatment of multiple symptoms, for examplea patient having both pure tone and noise-like tinnitus and/or a patienthaving both pain and paresthesia.

The predetermined site for stimulation using tonic and burst stimulationcan include, for example, peripheral neuronal tissue and/or centralneuronal tissue. Peripheral neuronal tissue can include a nerve root orroot ganglion or any peripheral neuronal tissue associated with a givendermatome or any neuronal tissue that lies outside the brain, brainstemor spinal cord. Peripheral nerves can include, but are not limited toolfactory nerve, optic nerve, oculomotor nerve, trochlear nerve,trigeminal nerve, abducens nerve, facial nerve, vestibulocochlear(auditory) nerve, glossopharyngeal nerve, vagal nerve, accessory nerve,hypoglossal nerve, occipital nerve (e.g., suboccipital nerve, thegreater occipital nerve, the lesser occipital nerve), the greaterauricular nerve, the lesser auricular nerve, the phrenic nerve, brachialplexus, radial axillary nerves, musculocutaneous nerves, radial nerves,ulnar nerves, median nerves, intercostal nerves, lumbosacral plexus,sciatic nerves, common peroneal nerve, tibial nerves, sural nerves,femoral nerves, gluteal nerves, thoracic spinal nerves, obturatornerves, digital nerves, pudendal nerves, plantar nerves, saphenousnerves, ilioinguinal nerves, gentofemoral nerves, and iliohypogastricnerves. Furthermore, peripheral neuronal tissue can include but is notlimited to peripheral nervous tissue associated with a dermatome. Anexemplary dermatome areas may comprise the C2/C3 dermatome area whichcomprises any peripheral nerve (e.g., the occipital nerve (the greater,the lesser, the third and the suboccipital nerve), the great auricularnerve, the transverse cervical nerve, the supraclavicular nerve, spinalaccessory nerve, phrenic nerve, dorsal scapular nerve) that arises fromthe C2 or C3 nerve root. Central neuronal tissue includes brain tissue,spinal tissue or brainstem tissue. Brain tissue can include prefrontalcortex, dorsal lateral prefrontal cortex, auditory cortex, somatosensorycortex, thalamus/sub-thalamus, basal ganglia, hippocampus, amygdala,hypothalamus, mammilary bodies, substantia nigra or cortex or whitematter tracts afferent to or efferent from the abovementioned braintissue, inclusive of the corpus callosum, more particularly, the braintissue includes the prefrontal cortex, auditory cortex and/orsomatosensory cortex. Yet further, brain tissue can include variousBrodmann Areas for example, but not limited to Brodmann Area 9, BrodmannArea 10, Brodmann Area 32, Brodmann Area 39, Brodmann Area 41, BrodmannArea 42, and Brodmann Area 46. Spinal tissue can include the ascendingand descending tracts of the spinal cord, more specifically, theascending tracts of that comprise intralaminar neurons or the dorsalcolumn. For example, the spinal tissue can include neuronal tissueassociated with any of the cervical vertebral segments (C1, C2, C3, C4,C5, C6, C7 and C8) and/or any tissue associated with any of the thoracicvertebral segments (T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12)and/or any tissue associated with any of the lumbar vertebral segments(L1, L2, L3, L4. L5, L6) and/or any tissue associated with the sacralvertebral segments (S1, S2, S3, S4, S5). More specifically, the spinaltissue is the dorsal column of the spinal cord. The brainstem tissue caninclude the medulla oblongata, pons or mesencephalon, more particularthe posterior pons or posterior mesencephalon, Lushka's foramen, andventrolateral part of the medulla oblongata.

As described below, one or more stimulation leads 14, as shown in FIGS.5A-5I, incorporated in stimulation system 10, as shown in FIGS. 4A and4B, includes one or more electrodes 18 adapted to be positioned near thepredetermined site or target tissue and used to deliver electricalstimulation energy to the predetermined site or target tissue inresponse to electrical signals received from stimulation source 12.Although various types of leads 14 are shown as examples, the presentapplication contemplates stimulation system 10 including any suitabletype of lead 14 in any suitable number and in any combination.

Medial or unilateral stimulation of the predetermined site may beaccomplished using a single electrical stimulation lead 14 implanted incommunication with the predetermined site, while bilateral electricalstimulation of the predetermined site may be accomplished using twostimulation leads 14 implanted in communication with the predeterminedsite on opposite sides of, for example, the spinal cord and or braintissue. Multi-site implantation of stimulation leads can be used.

Implantation of Stimulation Lead with Stimulation Electrodes (800)

One or more stimulation leads 14, as shown in FIGS. 5A-5I are implantedsuch that one or more stimulation electrodes 18 of each stimulation lead14 are positioned in communication with or in direct contact with oradjacent to the predetermined site. For the purposes described hereinand as those skilled in the art will recognize, when an embeddedstimulation system, such as the Bion®, is used, it is positioned similarto positioning the lead 14.

Techniques for implanting stimulation electrodes 18 are well known bythose of skill in the art and may be positioned in various body tissuesand in contact with various tissue layers; for example, deep brain,cortical, subdural, subarachnoid, epidural, cutaneous, transcutaneousand subcutaneous implantation is employed in some embodiments.

A. Brain

In certain embodiments, for example, patients who are to have anelectrical stimulation lead or electrode implanted into the brain,generally, first have a stereotactic head frame, such as the Leksell,CRW, or Compass, mounted to the patient's skull by fixed screws.However, frameless techniques may also be used. Subsequent to themounting of the frame, the patient typically undergoes a series ofmagnetic resonance imaging sessions, during which a series of twodimensional slice images of the patient's brain are built up into aquasi-three dimensional map in virtual space. This map is thencorrelated to the three dimensional stereotactic frame of reference inthe real surgical field. In order to align these two coordinate frames,both the instruments and the patient must be situated in correspondenceto the virtual map. The current way to do this is to rigidly mount thehead frame to the surgical table. Subsequently, a series of referencepoints are established to relative aspects of the frame and patient'sskull, so that either a person or a computer software system can adjustand calculate the correlation between the real world of the patient'shead and the virtual space model of the patient MRI scans. The surgeonis able to target any region within the stereotactic space of the brainwith precision (e.g., within 1 mm). Initial anatomical targetlocalization is achieved either directly using the MRI images orfunctional imaging (PET or SPECTscan, fMRI, MSI), or indirectly usinginteractive anatomical atlas programs that map the atlas image onto thestereotactic image of the brain. As is described in greater detailelsewhere in this application, the anatomical targets or predeterminedsite may be stimulated directly or affected through stimulation inanother region of the brain.

Based upon the coordinates, the electrical stimulation lead 14 can bepositioned in the brain. Typically, an insertion cannula for electricalstimulation lead 14 is inserted through the burr hole into the brain,but a cannula is not required. For example, a hollow needle may providethe cannula. The cannula and electrical stimulation lead 14 may beinserted together or lead 14 may be inserted through the cannula afterthe cannula has been inserted.

Once electrical stimulation lead 14 has been positioned in the brain,lead 14 is uncoupled from any stereotactic equipment present, and thecannula and stereotactic equipment are removed. Where stereotacticequipment is used, the cannula may be removed before, during, or afterremoval of the stereotactic equipment. Connecting portion 16 ofelectrical stimulation lead 14 is laid substantially flat along theskull. Where appropriate, any burr hole cover seated in the burr holemay be used to secure electrical stimulation lead 14 in position andpossibly to help prevent leakage from the burr hole and entry ofcontaminants into the burr hole.

Once electrical stimulation lead 14 has been inserted and secured,connecting portion 16 of lead 14 extends from the lead insertion site tothe implant site at which stimulation source 12 is implanted. Theimplant site is typically a subcutaneous pocket formed to receive andhouse stimulation source 12. The implant site is usually positioned adistance away from the insertion site, such as near the chest, below theclavicle or alternatively near the buttocks or another place in thetorso area. Once all appropriate components of stimulation system 10 areimplanted, these components may be subject to mechanical forces andmovement in response to movement of the person's body. A doctor, thepatient, or another user of stimulation source 12 may directly orindirectly input signal parameters for controlling the nature of theelectrical stimulation provided.

In addition to deep brain stimulation, cortical stimulation can also beused to stimulate various brain tissues, for example the auditorycortex. Various techniques for cortical stimulation are well known andused in the art, for example U.S. Pat. No. 7,302,298, which isincorporated herein by reference. The leads may be placed onto ordirectly into the target cortical tissue.

B. Spinal Cord and/or Peripheral Nerves

In certain embodiments, one or more stimulation electrodes 18 arepositioned in communication with the neuronal tissue of the spinal cord.Stimulation electrodes 18 are commonly positioned external to the duralayer surrounding the spinal cord. Stimulation on the surface of thecord is also contemplated, for example, stimulation may be applied tothe spinal cord tissue as well as to the nerve root entry zone.Stimulation electrodes 18 may be positioned in various body tissues andin contact with various tissue layers; for example, subdural,subarachnoid, epidural, and cutaneous, and/or subcutaneous implantationis employed in some embodiments.

Percutaneous leads commonly have two or more equally-spaced electrodeswhich are placed above the dura layer through the use of a Touhy-likeneedle. For insertion, the Touhy-like needle is passed through the skinbetween desired vertebrae to open above the dura layer. An example of aneight-electrode percutaneous lead is an OCTRODE® lead manufactured byAdvanced Neuromodulation Systems, Inc. A Bion® stimulation systemmanufactured by Advanced Bionics Corporation is also contemplated. Apercutaneous stimulation lead 14, such as example stimulation leads 14a-d, includes one or more circumferential electrodes 18 spaced apartfrom one another along the length of stimulating portion 20 ofstimulation lead 14. Circumferential electrodes 18 emit electricalstimulation energy generally radially (i.e., generally perpendicular tothe axis of stimulation lead 14) in all directions.

In contrast to the percutaneous leads, laminotomy leads have a paddleconfiguration and typically possess a plurality of electrodes (forexample, two, four, eight, or sixteen) arranged in one or more columns.A laminotomy, paddle, or surgical stimulation lead 14, such as examplestimulation leads 14 e-i, includes one or more directional stimulationelectrodes 18 spaced apart from one another along one surface ofstimulation lead 14. Directional stimulation electrodes 18 emitelectrical stimulation energy in a direction generally perpendicular tothe surface of stimulation lead 14 on which they are located. An exampleof a sixteen-electrode laminotomy lead is shown in FIG. 5H. Anotherexample of a laminotomy lead is an eight-electrode, two columnlaminotomy lead called the LAMITRODE® 44 lead, which is manufactured byAdvanced Neuromodulation Systems, Inc. Implanted laminotomy leads arecommonly transversely centered over the physiological midline of apatient. In such position, multiple columns of electrodes are wellsuited to address both unilateral and bilateral pain, where electricalenergy may be administered using either column independently (on eitherside of the midline) or administered using both columns to create anelectric field which traverses the midline. A multi-column laminotomylead enables reliable positioning of a plurality of electrodes, and inparticular, a plurality of electrode columns that do not readily deviatefrom an initial implantation position.

Laminotomy leads require a surgical procedure for implantation. Thesurgical procedure, or partial laminectomy, requires the resection andremoval of certain vertebral tissue to allow both access to the dura andproper positioning of a laminotomy lead. The laminotomy lead offers amore stable platform, which is further capable of being sutured in placethat tends to migrate less in the operating environment of the humanbody. Depending on the position of insertion, however, access to thedura may only require a partial removal of the ligamentum flavum at theinsertion site. In some embodiments, two or more laminotomy leads may bepositioned within the epidural space, and the leads may assume anyrelative position to one another.

C. Brainstem Stimulation

Implantation of a stimulation lead 14 in communication with thepredetermined brainstem area can be accomplished via a variety ofsurgical techniques that are well known to those of skill in the art.For example, an electrical stimulation lead can be implanted on, in, ornear the brainstem by accessing the brain tissue through a percutaneousroute, an open craniotomy, or a burr hole. Where a burr hole is themeans of accessing the brainstem, for example, stereotactic equipmentsuitable to aid in placement of an electrical stimulation lead 14 on,in, or near the brainstem may be positioned around the head. Anotheralternative technique can include, a modified midline or retrosigmoidposterior fossa technique.

In certain embodiments, electrical stimulation lead 14 is located atleast partially within or below the dura mater adjacent the brainstem.Alternatively, a stimulation lead 14 can be placed in communication withthe predetermined brainstem area by threading the stimulation lead upthe spinal cord column, as described above, which is incorporatedherein.

Yet further, a stimulation lead 14 can be implanted in communicationwith the predetermined brainstem area by a using stereotactic proceduressimilar to those described above, which are incorporated herein, forimplantation via the cerebrum.

Still further, a predetermined brainstem area can be indirectlystimulated by implanting a stimulation lead 14 in communication with acranial nerve (e.g., olfactory nerve, optic, nerve, oculomoter nerve,trochlear nerve, trigeminal nerve, abducent nerve, facial nerve,vestibulocochlear nerve, glossopharyngeal nerve, vagal nerve, accessorynerve, and the hypoglossal nerve) as well as high cervical nerves(cervical nerves have anastomoses with lower cranial nerves) such thatstimulation of a cranial nerve indirectly stimulates the predeterminedbrainstem tissue. Such techniques are further described in U.S. Pat.Nos. 6,721,603; 6,622,047; and 5,335,657 each of which are incorporatedherein by reference.

Coupling of Stimulation Source to Stimulation Lead (802)

In general terms, stimulation system 10 includes an implantableelectrical stimulation source 12 and one or more implantable electricalstimulation leads 14 for applying electrical stimulation pulses to apredetermined site. In operation, both of these primary components areimplanted in a subject's body, as discussed below. In certainembodiments, stimulation source 12 is coupled directly to a connectingportion 16 of stimulation lead 14. In other embodiments, stimulationsource 12 is incorporated into the stimulation lead 14 and stimulationsource 12 instead is embedded within stimulation lead 14. For example,such a stimulation system 10 may be a Bion® stimulation systemmanufactured by Advanced Bionics Corporation. Whether stimulation source12 is coupled directly to or embedded within the stimulation lead 14,stimulation source 12 controls the stimulation pulses transmitted to oneor more stimulation electrodes 18 located on a stimulating portion 20 ofstimulation lead 14, positioned in communication with a predeterminedsite, according to suitable stimulation parameters (e.g., duration,amplitude or intensity, frequency, pulse width, etc.).

In one embodiment, as shown in FIG. 4, stimulation system 10 comprisesimplantable pulse generator (IPG) 12, stimulation lead 14, controller26, and RF transmitter 24. IPG 12 typically comprises a metallic housingthat encloses the pulse generating circuitry, control circuitry,communication circuitry, battery, recharging circuitry, etc. of thedevice. An example commercially available IPG is the EON® IPG availablefrom Advanced Neuromodulation Systems, Inc. IPG 12 also typicallycomprises a header structure for electrically and mechanically couplingto stimulation lead 14. The electrical pulses generated by IPG 12 areconducted through conductors (not shown) embedded within stimulationlead 14 and delivered to tissue of the patient using electrodes 18 atdistal end 20 of stimulation lead 14. In another embodiment, the IPG canbe optimized for high frequency operation as described in U.S. PublishedApplication No. US20060259098, which is incorporated herein byreference. Furthermore, IPG 12 may be adapted to communicate withexternal devices, such as controller 26, after implantation within apatient. For example, controller 26 may utilize RF transmitter 22 toconduct wireless communications 24 with IPG 12 after IPG 12 is implantedwithin a patient to control the operations of IPG 12. Specifically, adoctor, the patient, or another user may use a controller 26 locatedexternal to the person's body to provide control signals for operationof IPG 12. Controller 26 provides the control signals to wirelesstransmitter 22, wireless transmitter 22 transmits the control signalsand power to the implanted pulse generator 12, and pulse generator 12uses the control signals to vary the stimulation parameters ofstimulation pulses transmitted through stimulation lead 14 to thepredetermined spinal column site. Wireless transmitter 22 and controller26 can be integrated within a single device and are commerciallydistributed with implantable pulse generator products.

Activate Stimulation Source and Transmit Stimulation Pulse (804)

Conventional neuromodulation devices can be modified to apply burst andtonic stimulation to nerve tissue of a patient by modifying the softwareinstructions and/or stimulation parameters stored in the devices.Specifically, conventional neuromodulation devices typically include amicroprocessor and a pulse generation module. The pulse generationmodule generates the electrical pulses according to a defined pulsewidth and pulse amplitude and applies the electrical pulses to definedelectrodes. The microprocessor controls the operations of the pulsegeneration module according to software instructions stored in thedevice and accompanying stimulation parameters. An example of acommercially available neuromodulation device that can be modified orprogrammed to apply burst stimulation, as well as, tonic stimulationincludes the EON®, manufactured by Advanced Neuromodulation Systems,Inc.

These conventional neuromodulation devices can be adapted by programmingthe microprocessor to deliver a number of spikes (relatively short pulsewidth pulses) that are separated by an appropriate inter-spike interval.Thereafter, the programming of the microprocessor causes the pulsegeneration module to cease pulse generation operations for aninter-burst interval. The programming of the microprocessor also causesa repetition of the spike generation and cessation of operations for apredetermined number of times. After the predetermined number ofrepetitions have been completed, the microprocessor can cause burststimulation to cease for an amount of time and resume thereafter.

Yet further, the microprocessor can be programmed to cause a tonic spikepulse interspersed in or around the burst stimulus. Also, in someembodiments, the microprocessor could be programmed to cause the pulsegeneration module to deliver a hyperpolarizing pulse before the firstspike of each group of multiple spikes.

The microprocessor can be programmed to allow the variouscharacteristics of the burst stimulus to be set by a physician to allowthe combination of the burst stimulus and tonic stimulus to be optimizedto treat the patient's disease. For example, the spike amplitude, theinter-spike interval, the inter-burst interval, the number of bursts tobe repeated in succession, the amplitude of the various pulses, theplacement and/or timing of the tonic stimulus in relation to the burststimulus, the amplitude of the tonic stimulus, the frequency of thetonic stimulus, the ratio of the burst stimulus to the tonic stimulus,altering the charge of the burst and/or tonic stimulus, altering the useof biopolar and/or unipolar or monopolar pulses (e.g., unipolar burststimulus and bipolar tonic stimulus or bipolar burst stimulus andunipolar tonic stimulus) and other such characteristics could becontrolled using respective parameters accessed by the microprocessorduring burst stimulus and/or tonic stimulus operations. These parameterscould be set to desired values by an external programming device viawireless communication with the implantable neuromodulation device.

FIG. 6 depicts a block diagram of IPG 600 that may be programmed todeliver burst and tonic stimulation in accordance with somerepresentative embodiments. IPG 600 comprises battery 601, pulsegenerating circuitry 602, output switch matrix 603, control circuitry604, and communication circuitry 605. Control circuitry 604 controls thegeneration of pulses by pulse generating circuitry 602 and the deliveryof the generated pulses by output switch matrix 603. Specifically,control circuitry 604 controls the amplitude and pulse width of arespective pulse by controlling pulse generating circuitry 602.Additionally, control circuitry 604 controls the timing of thegeneration of pulses by controlling pulse generating circuitry 602.Control circuitry 604 further configures output switch matrix 603 tocontrol the polarity associated with a plurality of outputs associatedwith switch matrix 603. In one representative embodiment, controlcircuitry 604 is implemented using a microprocessor and suitablesoftware instructions to implement the appropriate system control.Alternatively, control circuitry 604 may comprise an applicationspecific integrated circuit.

Control circuitry 604 preferably controls pulse generating circuitry 602and output switch matrix using “multi-stim set programs” which are knownin the art. A “stim set” refers to a set of parameters which define apulse to be generated. As shown in FIG. 6, a plurality of stim sets 606are defined in memory of IPG 200. Each stim set defines a pulseamplitude, a pulse width, a pulse delay, and an electrode combination.The pulse amplitude refers to the amplitude for a given pulse and thepulse width refers to the duration of the pulse. The pulse delayrepresents an amount of delay to occur after the generation of the pulse(equivalently, an amount of delay could be defined to occur before thegeneration of a pulse). The amount of delay represents an amount of timewhen no pulse generation occurs. The electrode combination defines thepolarities for each output of output switch matrix 603 which, thereby,controls how a pulse is applied via electrodes of a stimulation lead.Other pulse parameters could be defined for each stim set such as pulsetype, repetition parameters, etc.

As shown in FIG. 6, IPG 600 comprises a plurality of stimulationprograms 607. A stimulation program preferably defines a plurality ofpulses to be generated in succession and the frequency of repetition ofthe pulses. Specifically, when control circuitry 604 executes astimulation program, control circuitry 604 first retrieves thestimulation parameters for the first stimulation set of the stimulationprogram. Control circuitry 604 modifies an amplitude setting of pulsegenerating circuitry 602 according to the amplitude parameter of thestim set. Control circuitry 604 also configures output switch matrix 603according to the electrode combination of the stim set. Then, controlcircuitry 604 causes pulse generating circuitry 602 to generate a pulsefor an amount of time as defined by the pulse width parameter. Controlcircuitry 604 stops the pulse generation and waits an amount of timeequal to the pulse delay parameter. Control circuitry 604 then proceedsto the next stimulation set in the stimulation program and repeats theprocess. Each stimulation set in the stimulation program is processed inthe same manner. When the last stimulation set of the stimulation set iscompleted, control circuitry 604 waits an amount of time as defined bythe frequency parameter of the stimulation program before beginningagain. Then, control circuitry 604 generates another series of pulsesaccording to the various stim sets. Thereby, a pulse is generated foreach stim set according to the defined frequency of the stimulationprogram.

FIGS. 7 and 8 depict how stim sets and a stimulation program can bedefined to generate burst and tonic stimulation according to onerepresentative embodiment. FIG. 7 depicts a plurality of pulses 701-707.Pulses 701-705 are pulses of a discrete stimulation burst. The amplitudeof pulses 701-705 can be defined in the amplitude parameters (shown asPA₁ through PA₅) of a plurality of stim sets. Each pulse lasts for anamount of time which is defined by the pulse width parameters of theplurality of stim sets (shown as PW₁ through PW₅). The pulses are outputaccording the polarities of the electrode combinations (shown as EC₁through EC₅) of the stim sets. Preferably, each electrode combination ofthe burst stimulus is the same. The inter-pulse or inter-spike intervalsare defined by the delay parameters (shown as PD₁ through PD₄) of thestim sets.

A relatively small amount of delay is preferably defined to occur afterthe last pulse 705 of the burst stimulus before a charge balancing pulse706 occurs (to permit settling in the circuits of IPG 600 beforereversing polarity). The electrode combination (shown as EC₆) of thecharging balancing pulse 706 is preferably the opposite of the electrodecombination used for each pulse of the burst stimulus. That is, for eachanode of the burst stimulus, the charging balancing pulse 706 willconfigure those outputs as cathodes (and vice versa). Another delayoccurs after the charging balancing pulses 706 as defined by the delayparameter (shown as PD₆) for the respective stim set.

The last pulse 707 is a stimulation pulse for the tonic stimulation. Theamplitude of the tonic stimulation pulse is defined by the amplitudeparameter (shown as PA₇) of the respective stim set. The duration of thetonic stimulation pulse 707 is defined by the pulse width parameter(shown as PW₇) of the respective stim set. The tonic stimulation pulseis output according to the electrode combination of the respective stimset (shown as EC₇). The electrode combination of the tonic stimulationmay be the same as the electrode combination for the burst stimulationor may differ from the electrode combination for the burst stimulation.The delay parameter for the last stim set is not shown. Any suitablevalue could be assigned to the last stim set as long as the delay valuepermits a stimulation program to be repeated at an appropriatefrequency.

FIG. 8 depicts stimulation program 850 for the stimulation pattern shownin FIG. 7. Stimulation program 850 identifies stim sets SS1-SS7 asbelonging to the stimulation program. Accordingly, when stimulationprogram 850 is executed by IPG 600, stimulation pulses will besuccessively generated according to the parameters of the stim sets.Stimulation program 850 defines the frequency for the stimulationprogram, in this case, 40 Hz (although any suitable frequency could beselected). The burst stimulus and the tonic stimulus as defined by thesestim sets will be repeated according to the defined frequency parameter.

Referring again to FIG. 6, the parameters associated with the variousstim sets and stimulation programs are preferably communicated to IPG600 using communication circuitry 605. For example, an externalprogramming device may communicate the various parameters of the stimsets to IPG 600. Then, the external programming device may communicateparameters defining a given stimulation program according to the createdstim sets. It shall be appreciated that the parameters shown in FIGS.6-8 are by way of example only. Other parameters may be utilized todefine burst and/or tonic stimulation. For example, burst parameterscould be communicated from the programming device to IPG 600 (e.g.,burst amplitude, inter-pulse or inter-spike interval, intra-burst spikerepetition rate, pulse number, etc.), and IPG 600 could automaticallyconfigure parameters in its internal memory or registers in responsethereto.

In another embodiment, a neuromodulation device can be implemented toapply both burst and tonic stimulation using a digital signal processorand one or several digital-to-analog converters. The burst stimulusand/or tonic stimulus waveform could be defined in memory and applied tothe digital-to-analog converter(s) for application through electrodes ofthe medical lead. The digital signal processor could scale the variousportions of the waveform in amplitude and within the time domain (e.g.,for the various intervals) according to the various burst and/or tonicparameters. A doctor, the patient, or another user of stimulation source12 may directly or indirectly input stimulation parameters to specify ormodify the nature of the stimulation provided.

In certain embodiments, the stimulation parameters may comprise a burststimulation having a frequency in the range of about 1 Hz to about 300Hz in combination with a tonic stimulation having a frequency in therange of about 1 Hz to about 300 Hz. Those of skill in the art realizethat the frequencies can be altered depending upon the capabilities ofthe IPGs that are utilized. More particularly, the burst stimulation maybe at about 6, 18, 40, 60, 80, 100, 150, 200, 250 or 300 Hz consistingof 5 spikes with 1 ms pulse width, 1 ms interspike interval incombination with about 6, 18, 40, 60, 80, 100, 150, 200, 250, 300 Hztonic stimulation interspersed between or around the bursts, or anyvariation thereof depending upon the efficacy of treatment and thecapabilities of the IPG.

Yet further, the initial stimulation protocol in step 804 can be anon-saturating stimulation protocol that only partially eliminates atleast one symptom associated with the neurological disorder/disease. Forexample, a non-saturating protocol may be created by employing voltagesor stimulation protocols known not to be completely effective ineliminating neurological disorder/disease. Using such non-saturatingprotocols, a location of maximum efficacy may be ascertained, withregards to the location of stimulation lead 14 and/or the differentialactivation of various stimulation electrodes 18. For example, astimulation protocol may be designed for the patient at step 804 whereina voltage is applied that only partially eliminate the neurologicaldisorder/disease, and various stimulation parameters are tested in orderto determine a protocol of maximum efficacy. Once an optimal locationand protocol have been determined, the voltage or current may beadjusted to completely eliminate the neurological disorder/disease. Inother embodiments, step 804 may include the application of a saturatingstimulation protocol that reduces or alleviates the neurologicaldisorder/disease. Similar to non-saturating protocols, saturatingprotocols can also be employed in step 804 such that the saturatingstimulation protocol eliminates or alleviates at least one symptomassociated with the neurological disorder/disease.

Still further, the initial stimulation protocol in step 804 may employthe use of either tonic and/or burst stimulation to determine thelocation of maximum efficacy with regards to the location of stimulationlead 14 and/or activation or various stimulation electrodes 18. Once thelocation of maximum efficacy is determined, then a stimulation protocolutilizing both tonic and burst stimulation can be employed to reduce oralleviate at least one symptom associated the neurologicaldisorder/disease.

Trial Assessment (806)

In some embodiments, it is considered that several cycles ofintra-implantation trials may be required. In preferred embodiments, acomparison of the patient's symptoms between multiple cycles ofintra-implantation trial stimulation will be used to determine theoptimal location and stimulation protocol. In further embodiments, steps804 through 808 represent a repetitive cycle that ends when an optimallocation and protocol have been selected. In some embodiments, once thestimulation lead 14 has been properly positioned such that subject'ssymptoms are improved or absent, intra-implantation trial stimulationmay be considered complete. It is contemplated that stimulationparameters may be modified to maximize the effectiveness of the therapyboth prior to and subsequent to the end of the intra-implantation trialstimulations.

Those skilled in the art recognize that there are many methods to assessvarious improvements of symptoms associated with neurologicaldisorders/diseases.

1. Tinnitus

A subject is administered a therapeutically effective stimulation sothat the subject has an improvement in the parameters relating totinnitus including informal questioning of the subject, formalsubjective testing and analysis according to one or more audiology test,for example the Goebel tinnitus questionnaire or other validatedtinnitus questionnaires, audiometry, tinnitus matching, impedence, BAEP,and OAE. The improvement is any observable or measurable improvement.Thus, one of skill in the art realizes that a treatment may improve thepatient condition, but may not be a complete cure of the disease.

2. Pain

One example of a method for pain measurement is the use of the VisualAnalog Scale (VAS). In the VAS patients are asked to rank their pain bymaking a mark on a bar that is labeled “no pain” on one end, and “painas bad as possible” on the other end. Patients may mark the bar anywherebetween the two opposite poles of perceived pain sensation. This markcan then be given any quantitative value such as fractional, decimal, orinteger values by the clinician and used as a semi-quantitative painmeasurement. In various tests for pain severity, patients may rank theirpain on a scale between zero and ten, by a scale of faces depictingvarious emotions from happy to very sad and upset, and by answering avariety of questions describing the pain. In preferred embodiments, thepatient's pain is assessed prior to and during the trial implantationprocedure, for example prior to process 800, and then again at process806. In other embodiments, informal subjective questioning of theperson, and/or formal subjective testing and analysis may be performedto determine whether the subject's pain has sufficiently improvedthroughout the intra-implantation trial stimulation.

In addition to utilizing pain scores and grading and objective measuresincluding use of additional pain medications (e.g., reduction in theamount of medication consume or elimination of the consumption of painmedications), other methods to determine improvement of a patient's painmay comprise administering various standardized questionnaires or teststo determine the patient's neuropsychological state.

3. Neuropsychological Tests

Thus, a subject is administered a therapeutically effective stimulationso that the subject has an improvement in the parameters relating to theneurological disorder or condition including subjective measures suchas, for example, neurological examinations and neuropsychological tests(e.g., Minnesota Multiphasic Personality Inventory, Beck DepressionInventory, Mini-Mental Status Examination (MMSE), Hamilton Rating Scalefor Depression, Wisconsin Card Sorting Test (WCST), Tower of London,Stroop task, MADRAS, CGI, N-BAC, or Yale-Brown Obsessive Compulsivescore (Y-BOCS)), motor examination, and cranial nerve examination, andobjective measures including use of additional psychiatric medications,such as anti-depressants, or other alterations in cerebral blood flow ormetabolism and/or neurochemistry.

Patient outcomes may also be tested by health-related quality of life(HRQL) measures: Patient outcome measures that extend beyond traditionalmeasures of mortality and morbidity, to include such dimensions asphysiology, function, social activity, cognition, emotion, sleep andrest, energy and vitality, health perception, and general lifesatisfaction. (Some of these are also known as health status, functionalstatus, or quality of life measures.)

In certain embodiments, in connection with improvement in one or more ofthe above or other neurological disorders, the electrical stimulationmay have a “brightening” effect on the person such that the person looksbetter, feels better, moves better, thinks better, and otherwiseexperiences an overall improvement in quality of life.

Adjustment of Stimulation Parameters and/or Lead Location (808)

If the subject's neurological disorder/disease has not sufficientlyimproved at process 806, or if the reduction of the neurologicaldisorder/disease is determined to be incomplete or inadequate during theintra-implantation trial stimulation procedure, stimulation lead 14 maybe moved incrementally or even re-implanted, one or more stimulationparameters may be adjusted, or both of these modifications may be madeat process 808 and the trial stimulation and analysis repeated until atleast one symptom associated with the neurological disorder/disease hasimproved.

Implantation of Stimulation Source (810)

In some embodiments the intra-trial stimulation period is determined tobe complete during process 806. In other embodiments, theintra-implantation trial stimulation is not performed, and the methodproceeds from process 802 to 810. Once the location for the stimulationlead 14 has been determined, the stimulation lead may be properlyimplanted and secured and a stimulation source 12 may be surgicallyimplanted at process 810. Techniques for implanting stimulation sourcessuch as stimulation source 12 are known to those skilled in the art. Fornon-embedded systems, the implant site is typically a subcutaneouspocket formed to receive and house stimulation source 12. The implantsite is usually located some distance away from the insertion site, suchas in or near the lower back or buttocks.

Tunneling of Stimulation Lead to Stimulation Source (812)

Where stimulation lead 14 includes connecting portion 16, connectingportion 16 may be tunneled, at least in part, subcutaneously to theimplant site of stimulation source 12 at step 812. Some embodiments mayuse a non-implantable stimulation source.

Input of Parameters to Stimulation Source (814)

During process 814, a doctor, the patient, or another user ofstimulation source 12 may directly or indirectly input stimulationparameters for controlling the nature of the electrical stimulationprovided to the target tissue area or predetermined area, if not alreadyset during any intra-implantation trial stimulation period. If themethod proceeds from 802 to 810, then the procedure for setting theparameters in step 814 follows the protocol as described above for step804. Where appropriate, post-implantation trial stimulation may beconducted to determine the efficacy of various types of burst and tonicstimulation. Examples of efficacy metrics may include the minimumrequired voltage for a given protocol to achieve maximum and/ortherapeutic benefits to the neurological disease and/or disorder.Efficacy metrics may also include a measurement of the presence and/ordegree of habituation to a given protocol over one or more weeks ormonths, and any necessary modifications made accordingly. Suchassessments can be conducted by suitable programming, such as thatdescribed in U.S. Pat. No. 5,938,690, which is incorporated by referencehere in full. Utilizing such a program allows an optimal stimulationtherapy to be obtained at minimal power. This ensures a longer batterylife for the implanted systems.

In certain embodiments, it may be desirable for the patient to controlthe therapy to optimize the operating parameters to achieve increased oroptimized the treatment. For example, the patient can alter the pulsefrequency, pulse amplitude and pulse width using a hand held radiofrequency device that communicates with the IPG. Once the operatingparameters have been altered by the patient, the parameters can bestored in a memory device to be retrieved by either the patient or theclinician. Yet further, particular parameter settings and changestherein may be correlated with particular times and days to form apatient therapy profile that can be stored in a memory device.

Following post-implantation, the efficacy of the system can bedetermined by utilizing any of the any method well known and describedto assess various improvements of symptoms associated with neurologicaldisorders/diseases. Exemplary methods are described above under step 806and incorporated herein by reference.

Although example steps are illustrated and described, the claimedmaterial contemplates two or more steps taking place substantiallysimultaneously or in a different order. In addition, the claimedmaterial contemplates using methods with additional steps, fewer steps,or different steps, so long as the steps remain appropriate forimplanting stimulation system 10 into a person for electricalstimulation of the a predetermined site.

IV. Types of Neurological Conditions

Accordingly, the present application relates to modulation of neuronalactivity to affect neurological, neuropsychological or neuropsychiatricactivity. The present application finds particular application in themodulation of neuronal function or processing to affect a functionaloutcome. The modulation of neuronal function is particularly useful withregard to the prevention, treatment, or amelioration of neurological,psychiatric, psychological, conscious state, behavioral, mood, andthought activity (unless otherwise indicated these will be collectivelyreferred to herein as “neurological activity” which includes“psychological activity” or “psychiatric activity”). When referring to apathological or undesirable condition associated with the activity,reference may be made to a neurological disorder which includes“psychiatric disorder” or “psychological disorder” instead ofneurological activity or psychiatric or psychological activity. Althoughthe activity to be modulated usually manifests itself in the form of adisorder such as a attention or cognitive disorders (e.g., AutisticSpectrum Disorders); mood disorder (e.g., major depressive disorder,bipolar disorder, and dysthymic disorder) or an anxiety disorder (e.g.,panic disorder, posttraumatic stress disorder, obsessive-compulsivedisorder and phobic disorder); neurodegenerative diseases (e.g.,multiple sclerosis, Alzheimer's disease, amyotrophic lateral sclerosis(ALS), Parkinson's disease, Huntington's Disease, Guillain-Barresyndrome, myasthenia gravis, and chronic idiopathic demyelinatingdisease (CID)), movement disorders (e.g., dyskinesia, tremor, dystonia,chorea and ballism, tic syndromes, Tourette's Syndrome, myoclonus,drug-induced movement disorders, Wilson's Disease, ParoxysmalDyskinesias, Stiff Man Syndrome and Akinetic-Ridgid Syndromes andParkinsonism), epilepsy, tinnitus, pain, phantom pain, diabetesneuropathy, one skilled in the art appreciates that some methods oftreatment may also find application in conjunction with enhancing ordiminishing any neurological or psychiatric function, not just anabnormality or disorder. Neurological activity that may be modulated caninclude, but not be limited to, normal functions such as alertness,conscious state, drive, fear, anger, anxiety, repetitive behavior,impulses, urges, obsessions, euphoria, sadness, and the fight or flightresponse, as well as instability, vertigo, dizziness, fatigue,photofobia, concentration dysfunction, memory disorders, headache,dizziness, irritability, fatigue, visual disturbances, sensitivity tonoise (misophonia, hyperacusis, phonofobia), judgment problems,depression, symptoms of traumatic brain injury (whether physical,emotional, social or chemical), autonomic functions, which includessympathetic and/or parasympathetic functions (e.g., control of heartrate), somatic functions, and/or enteric functions. Thus, the presentapplication encompasses modulation of central and/or peripheral nervoussystems.

Other neurological disorders can include, but are not limited toheadaches, for example, migraine, trigeminal autonomic cephalgia(cluster headache (episodic and chronic)), paroxysmal hemicrania(epidsodic and chronic), hemicrania continua, SUNCT (shortlastingunilateral neuralgiform headache with conjunctival injection andtearing), cluster tic syndrome, trigenminal neuroalgia, tension typeheadache, idiopathic stabbing headache, etc. The neurostimulation devicecan be implanted intracranially or peripherally, for example, but notlimited to implanting a neurostimulation device occipitally for thetreatment of headaches.

Autonomic and/or enteric nervous system disorders that can be treatedusing the stimulation system and/or certain representative methods oftreatment include, but are not limited to hypertension, neurosis cordisor heart rhythm disorders, obesity, gastrointestinal motion disorders,respiratory disorders, diabetes, sleep disorders, snoring, incontinenceboth urologic and gastrointestinal, sexual dysfunction, chronic fatiguesyndrome, fibromyalgia, whiplash associated symptoms, post-concussionsyndrome, posttraumatic stress disorder etc.

Yet further immunological disorders may also be treated using thestimulation system and/or representative methods of treatment. This isbased on the fact that the immune system senses antigens coordinatesmetabolic, endocrine and behavioral changes that support the immunesystem and modulates the immune system via neuroendocrine regulation anddirect immune cell regulation. Such immunological disorders include,such as allergy, rhinitis, asthma, rheumatoid arthritis, psoriasisarthritis, lupus erythematosus disseminatus, multiple sclerosis andother demyelinating disorders, autoimmune thyroiditis, Crohn's disease,diabetis melitus etc.

Yet further tumoral disorders, both malignant and benign may also betreated using the stimulation system and/or some representative methodsof treatment. This is based on the fact that tumoral behavior is linkedto immunological function. This is seen in immunodeficiency syndromessuch as AIDS and hematological disorders, where multiple and differenttumors develop. In this setting neuromodulation could indirectlyinfluence tumoral behavior.

Yet further neuroendocrine disorders may also be treated using thestimulation system and/or some representative methods of treatment. Suchdisorders are stress reactions, hypothalamic-pituitary axis dysfunction,etc.

Yet further functional disorders may also be treated using thestimulation system and/or some representative methods of treatment. Suchdisorders can be anorexia, boulemia, phobias, addictions, paraphilia,psychosis, depression, bipolar disorder, kleptomania, aggression, orantisocial sexual behavior. One skilled in the art appreciates that somerepresentative embodmients may also find application in conjunction withenhancing or diminishing any neurological or psychiatric function, notjust an abnormality or disorder.

Some representative neuromodulation methods of treatment can be used toalter a physiological and/or pathological signaling pattern. Thus, it isenvisioned that the stimulation method as used herein can alter suchpatterns to alleviate the neurological condition or disease, or toimprove or enhance a desired physiological function (e.g., selfconfidence, alleviating shyness, distrust etc).

In certain embodiments, the neuromodulation method can be used to treatneurological disorders or diseases that result from incorrect centralnervous system control in which the disorder comprises a regularbursting rhythm. Such disorders having a regular bursting rhythminclude, but are not limited to Parkinson's, epilepsy, tinnitus andphantom pain or other forms of deafferentation or central pain. Thus, itis envisioned that some representative methods of neuromodulation willalter or disrupt the regular bursting rhythm associated with thedisorder.

Still further, it is known that the sympathetic system fires in bursts,and the parasympathetic system as well. Any neurological ornon-neurological disorder associated with a hypoactive, hyperactive ormaladaptive sympathetic or parasympathetic firing can be modified usingthis method.

Still further, the neuromodulation method can be used to treatneurological disorders or diseases that result from incorrect centralnervous system control in which the disorder comprises an irregularbursting rhythm. Such disorders can include, but are not limited todystonia or chorea or hallucinations. Thus, it is envisioned that suchconditions are caused or linked to arrhythmic burst firing ordesynchronized tonic firing can be treated utilizing some representativeneuromodulation systems and/or stimulation parameters.

In different motor, sensory and autonomic neurological disorders twomechanisms might be involved: the firing rate is altered in tonic andburst firing cells and the amount of burst firing is increased. A secondmechanism involved is an alteration in the synchrony of neuronal firing,which is often increased.

REFERENCES CITED

All patents and publications mentioned in the specifications areindicative of the levels of those skilled in the art. All patents andpublications are herein incorporated by reference to the same extent asif each individual publication was specifically and individuallyindicated to be incorporated by reference.

-   U.S. Application No. 60/528,604-   U.S. Application No. 60/528,689-   U.S. Pat. No. 5,335,657-   U.S. Pat. No. 5,938,690-   U.S. Pat. No. 6,567,696-   U.S. Pat. No. 6,622,047-   U.S. Pat. No. 6,671,555-   U.S. Pat. No. 6,690,974-   U.S. Pat. No. 6,721,603-   U.S. Pat. No. 6,740,072-   U.S. Pat. No. 6,748,276-   Alain, C., D. L. Woods, et al., (1998). Brain Res 812(1-2): 23-37.-   Alho, K. (1995). Ear Hear 16(1): 38-51.-   Bandrowski, A. E., S. L. Moore, et al., (2002). Synapse 44(3):    146-57.-   Beurrier, C., P. Congar, et al., (1999). J Neurosci 19(2): 599-609.-   Binder, Adv Exp Med. Biol. 2004; 548:34-56.-   Brozoski, T. J., C. A. Bauer, et al., (2002). J Neurosci 22(6):    2383-90.-   Brumberg, The Journal of Neuroscience, 20 (13):4829-4843), 2000-   Brumberg, The Journal of Neuroscience, Jul. 1, 2000,    20(13):4829-4843.-   Cazals, Y., K. C. Horner, et al., (1998). J Neurophysiol 80(4):    2113-20.-   Chen, G. D. and P. J. Jastreboff (1995). Hear Res 82(2): 158-78.-   Chemigovskii, V. N., S. S. Musyashchikova, et al., (1979). Biol Bull    Acad Sci USSR 6(1): 1-7.-   Condon, C. D. and N. M. Weinberger (1991). Behav Neurosci 105(3):    416-30.-   Cooper, D. C. (2002). Neurochem Int 41(5): 333-40.-   Coro, F., P. E. M, et al., (1998). J Exp Biol 201(Pt 20): 2879-2890.-   Coutinho, V. and T. Knopfel (2002). Neuroscientist 8(6): 551-61.-   De Ridder, D., G. De Mulder, et al. (2005). ORL in press.-   De Ridder, D., E. Verstraeten, et al. (2005). 0 to 1 Neurotol 26(4):    616-619.-   De Ridder, D. et al., (2007a). Int. J. Med. Sci. 2007 4(5):237-241.-   De Ridder, D. et al., (2007b). Int. J. Med. Sci. 2007 4(5):242-246.-   Huang, Y. Z., M. J. Edwards, et al. (2005). Neuron 45(2): 201-6.-   Plewnia, C., M. Bartels, et al. (2003). Ann Neurol 53(2): 263-6.-   Csepe, V., G. Karmos, et al., (1987). Electroencephalogr Clin    Neurophysiol 66(6): 571-8.-   Deouell, L. Y., S. Bentin, et al., (1998). Psychophysiology 35(4):    355-65.-   Diamond, D. M. and N. M. Weinberger (1984). Behav Neurosci 98(2):    189-210.-   Disney, A. and M. B. Calford (2001). J Neurophysiol 86(2): 1052-6.-   Edeline, J. M., N. Neuenschwander-el Massioui, et al., (1990). Behav    Brain Res 39(2): 145-55.-   Edeline, J. M., Y. Manunta, et al., (2000). J Neurophysiol 84(2):    934-52.-   Eggermont, J. J. (1990). Hear Res 48(1-2): 111-23.-   Eggermont, J. J. (2003). Auris Nasus Larynx 30 Suppl: S7-12.-   Eggermont, J. J. and M. Kenmochi (1998). Hear Res 117(1-2): 149-60.-   Fairhall, A. L., G. D. Lewen, et al., (2001). Nature 412(6849):    787-92.-   Feig, S. L. (2004). J Comp Neurol 468(1): 96-111.-   Fischer, C., D. Morlet, et al., (2000). Audiol Neurootol 5(3-4):    192-7.-   Franceschetti et al., Brain Res. 1995 Oct. 23; 696(1-2):127-39.-   Futatsugi, Y. and J. J. Riviello, Jr. (1998). Brain Dev 20(2): 75-9.-   Gerken, G. M. (1996). Hear Res 97(1-2): 75-83.-   Givois, V. and G. S. Pollack (2000). J Exp Biol 203 Pt 17: 2529-37.-   Gopal, K. V. and G. W. Gross (2004). Hear Res 192(1-2): 10-22.-   Gray and Singer, Proc Natl Acad Sci USA. 1989 March; 86(5):1698-702.-   Guatteo et al., Brain Res. 1996 Nov. 25; 741(1-2):1-12.-   He, J. (1997). J Neurophysiol 77(2): 896-908.-   He, J. (2003). Exp Brain Res 153(4): 579-90.-   He, J. and B. Hu (2002). J Neurophysiol 88(4): 2152-6.-   He, J., Y. Q. Yu, et al., (2002). J Neurophysiol 88(2): 1040-50.-   Hsieh, C. Y., S. J. Cruikshank, et al., (2000). Brain Res 880(1-2):    51-64.-   Hu, B. (1995). J Physiol 483 (Pt 1): 167-82.-   Hu, B., V. Senatorov, et al., (1994). J Physiol 479 (Pt 2): 217-31.-   Huguenard, J. R. (1999). Adv Neurol 79: 991-9.-   Jastreboff, P. J. (1990). Neurosci Res 8(4): 221-54.-   Jastreboff, P. J. and C. T. Sasaki (1986). J Acoust Soc Am 80(5):    1384-91.-   Jastreboff, P. J., J. F. Brennan, et al., (1988). Laryngoscope    98(3): 280-6.-   Javitt, D. C., M. Steinschneider, et al., (1994). Brain Res 667(2):    192-200.-   Javitt, D. C., M. Steinschneider, et al., (1996). Proc Natl Acad Sci    USA 93(21): 11962-7.-   Jeanmonod, D., M. Magnin, et al., (1996). Brain 119 (Pt 2): 363-75.-   Joliot et al., Proc Natl Acad Sci USA. 1994 Nov. 22;    91(24):11748-51.-   Jongsma, M. L., C. M. Van Rijn, et al., (1998). Eur J Pharmacol    341(2-3): 153-60.-   Kaltenbach, J. A. and C. E. Afman (2000). Hear Res 140(1-2): 165-72.-   Kaltenbach, J. A., D. A. Godfrey, et al., (1998). Hear Res 124(1-2):    78-84.-   Kaltenbach, J. A., M. A. Zacharek, et al., (2004). Neurosci Lett    355(1-2): 121-5.-   Kawaguchi, Y. and Y. Kubota (1993). J Neurophysiol 70(1): 387-96.-   Kelly, J. B. and H. Zhang (2002). Hear Res 168(1-2): 35-42.-   Kepecs, A. and J. Lisman (2003). Network 14(1): 103-18.-   Kepecs, A., X. J. Wang, et al., (2002). J Neurosci 22(20): 9053-62.-   Kraus, N., T. McGee, et al., (1992). Ear Hear 13(3): 158-64.-   Kraus, N., T. McGee, et al., (1994). J Neurophysiol 72(3): 1270-7.-   LeDoux, J. E., A. Sakaguchi, et al., (1984). J Neurosci 4(3):    683-98.-   Lee et al., J. Neurosci. 2001 Mar. 1; 21(5):1757-66.-   Lever et al., J. Neurosci. 2001 Jun. 15; 21(12):4469-77.-   Lisman, J. E. (1997). Trends Neurosci 20(1): 38-43.-   Ma, C. L., J. B. Kelly, et al., (2002). Hear Res 168(1-2): 25-34.-   Martin, W. H., J. W. Schwegler, et al., (1993). Laryngoscope 103(6):    600-4.-   Massaux, A. and J. M. Edeline (2003). Exp Brain Res 153(4): 573-8.-   Massaux, A., G. Dutrieux, et al., (2004). J Neurophysiol 91(5):    2117-34.-   Mattia et al., Hippocampus. 1997; 7(1):48-57.-   Matveev, Cerebral Cortex, Vol. 10, No. 11, 1143-1153, November 2000.    McAlonan and Brown, Neuroscientist. 2002 August; 8(4):302-5.-   McCormick, D. A. and H. R. Feeser (1990). Neuroscience 39(1):    103-13.-   McCormick, D. A. and M. von Krosigk (1992). Proc Natl Acad Sci USA    89(7): 2774-8.-   Miller, L. M., M. A. Escabi, et al., (2001). J Neurosci 21(20):    8136-44.-   Miller, L. M., M. A. Escabi, et al., (2001). Neuron 32(1): 151-60.-   Moller, A. R. (1984). Ann 0 to 1 Rhinol Laryngol 93(1 Pt 1): 39-44.-   Mooney, D. M., L. Zhang, et al., (2004). Proc Natl Acad Sci USA    101(1): 320-4.-   Muller, J. R., A. B. Metha, et al., (1999). Science 285(5432):    1405-8.-   N. Urbain, et al., J. Neurosci., Oct. 1, 2002; 22(19): 8665-8675-   Naatanen, R. (1992). Attention and brain function. Hillsdale, N.J.,    Lawrence Erlbaum.-   Naatanen, R. (2001). Psychophysiology 38(1): 1-21.-   Naatanen, R., P. Paavilainen, et al., (1993). Psychophysiology    30(5): 436-50.-   Nousak, J. M., D. Deacon, et al., (1996). Brain Res Cogn Brain Res    4(4): 305-17.-   Ochi, K. and J. J. Eggermont (1996). Hear Res 95(1-2): 63-76.-   Ochi, K. and J. J. Eggermont (1997). Hear Res 105(1-2): 105-18.-   Ohzawa, I., G. Sclar, et al., (1985). J Neurophysiol 54(3): 651-67.-   Oleskevich, S, and B. Walmsley (2002). J Physiol 540(Pt 2): 447-55.-   Pantev, C., H. Okamoto, et al., (2004). Eur J Neurosci 19(8):    2337-44.-   Perez-Reyes, E. (2003). Physiol Rev 83(1): 117-61.-   Poremba, A., D. Jones, et al., (1998). Eur J Neurosci 10(10):    3035-43.-   Puel, J. L. (1995). Prog Neurobiol 47(6): 449-76.-   Puel, J. L., J. Ruel, et al., (2002). Audiol Neurootol 7(1): 49-54.-   Ramcharan, E. J., C. L. Cox, et al., (2000). J Neurophysiol 84(4):    1982-7.-   Ritter, W., D. Deacon, et al., (1995). Ear Hear 16(1): 52-67.-   Romanski, L. M. and J. E. LeDoux (1992). J Neurosci 12(11): 4501-9.-   Sakurai, Y. (1990). Behav Neurosci 104(2): 253-63.-   Sakurai, Y. (2002). Neuroscience 115(4): 1153-63.-   Sanes, D. H., J. McGee, et al., (1998). J Neurophysiol 80(1):    209-17.-   Schwarz, D. W., F. Tennigkeit, et al., (2000). Acta Otolaryngol    120(2): 251-4.-   Schwindt and Crill, J. Neurophysiol. 1999 March; 81(3):1341-54.    Sherman, S. M. (2001). Nat Neurosci 4(4): 344-6.-   Sherman and Guillery, Neuron. 2002 Jan. 17; 33(2):163-75.-   Sherman and Guillery, Philos Trans R Soc Lond B Biol Sci. 2002 Dec.    29; 357(1428):1695-708.-   Sherman and Guillery, Philos Trans R Soc Lond B Biol Sci. 2002 Dec.    29; 357(1428):1809-21.-   Sherman, S. M. (2001). Trends Neurosci 24(2): 122-6.-   Steriade, M. and R. R. Llinas (1988). Physiol Rev 68(3): 649-742.-   Steriade, M., D. Pare, et al., (1989). J Neurosci 9(7): 2215-29.-   Steriade, Neuroscience. 2000; 101(2):243-76.-   Suga, N., Y. Zhang, et al., (1997). J Neurophysiol 77(4): 2098-114.-   Swadlow, H. A. and A. G. Gusev (2001). Nat Neurosci 4(4): 402-8.-   Tabak, J. and P. E. Latham (2003). Neuroreport 14(11): 1445-9.-   Tennigkeit, F., D. W. Schwarz, et al., (1996). J Neurophysiol 76(6):    3597-608.-   Tennigkeit, F., E. Puil, et al., (1997). Acta Otolaryngol 117(2):    254-7.-   Tiitinen, H., K. Alho, et al., (1993). Psychophysiology 30(5):    537-40.-   Traub et al., J. Physiol. 1994 Nov. 15; 481 (Pt 1):79-95.-   Ulanovsky, N., L. Las, et al., (2003). Nat Neurosci 6(4): 391-8.-   van Vreeswijk, C. and D. Hansel (2001). Neural Comput 13(5): 959-92.-   Wan et al., Neuroscience. 2004; 125(4):1051-60.-   Webster, W. R. (1971). Electroencephalogr Clin Neurophysiol 30(4):    318-30.-   Weinberger, N. M. (1998 Neurobiol Learn Mem 70(1-2): 226-51.-   Weinberger, N. M. (2004). Nat Rev Neurosci 5(4): 279-90.-   Weinberger, N. M. and J. S. Bakin (1998). Audiol Neurootol 3(2-3):    145-67.-   Wong and Stewart, J. Physiol. 1992 November; 457:675-87.-   Wu, S. H., C. L. Ma, et al., (2004). J Neurosci 24(19): 4625-34.-   Zacharek, M. A., J. A. Kaltenbach, et al., (2002). Hear Res    172(1-2): 137-43.-   Zhang, J. S, and J. A. Kaltenbach (1998). Neurosci Lett 250(3):    197-200.-   Zhang, Y., N. Suga, et al., (1997). Nature 387(6636): 900-3.

Although certain representative embodiments and advantages have beendescribed in detail, it should be understood that various changes,substitutions and alterations can be made herein without departing fromthe spirit and scope of the appended claims. Moreover, the scope of thepresent application is not intended to be limited to the particularembodiments of the process, machine, manufacture, composition of matter,means, methods and steps described in the specification. As one ofordinary skill in the art will readily appreciate when reading thepresent application, other processes, machines, manufacture,compositions of matter, means, methods, or steps, presently existing orlater to be developed that perform substantially the same function orachieve substantially the same result as the described embodiments maybe utilized. Accordingly, the appended claims are intended to includewithin their scope such processes, machines, manufacture, compositionsof matter, means, methods, or steps.

What is claimed is:
 1. A method of stimulating nerve tissue of a patientusing an implantable pulse generator, the method comprising: storing, inthe implantable pulse generator, one or more first stimulationparameters that define at least one stimulation pulse to be repeated ina tonic manner; storing, in the implantable pulse generator, one or moresecond stimulation parameters that define stimulation pulses to berepeated in bursts; generating, by the implantable pulse generator, acombination of burst stimulation and tonic stimulation according to thefirst and second stimulation parameters, providing the burst and tonicstimulation from the implantable pulse generator to a stimulation lead;and applying the burst and tonic stimulation to nerve tissue of thepatient via one or more electrodes of the stimulation lead.
 2. Themethod of claim 1, wherein the first and second parameters arestimulation program parameters that are repeated in stimulation cyclesby the implantable pulse generator.
 3. The method of claim 1, whereinthe burst and tonic stimulation are applied to nerve tissue of thepatient using different electrode combinations.
 4. The method of claim1, wherein the generating generates a respective pulse for the tonicstimulation immediately before beginning pulses for an individual burstof the burst stimulation.
 5. The method of claim 1 further whereinpulses for the tonic stimulation are generated between an occurrence ofa first pulse of a respective burst and a last burst of the respectiveburst of the burst stimulation.
 6. The method of claim 1, wherein theneurological disorder is a movement disorder.
 7. The method of claim 1,wherein the neurological disorder is a sensory disorder.
 8. The methodof claim 7, wherein the sensory disorder is tinnitus or pain.
 9. Amethod of treating tinnitus comprising the steps of: implanting at leastan electrical lead within a patient such that at least one electrode ofthe electrical lead is disposed adjacent to central neuronal tissue;selecting one or more operating parameters for an electrical stimulationsystem that define burst stimulation in combination with tonicstimulation that is effective for treating tinnitus; programming theelectrical stimulation system to generate electrical pulses according toone or more operating parameters; and activating the electricalstimulation system to deliver electrical pulses to the electrodeadjacent to nervous tissue thereby treating the patient's tinnitus. 10.The method of claim 9, wherein central nervous tissue is associated withthe patient's spinal cord.
 11. The method of claim 9, wherein thecentral nervous tissue is associated with the cortex.
 12. The method ofclaim 11, wherein the cortex is the auditory cortex.
 13. The method ofclaim 9, wherein the one or more operating parameters include a pulseamplitude parameter, a pulse width parameter, and a frequency parameter,wherein the frequency parameter defines a frequency for the repetitionof bursts, the pulse amplitude parameter defining a pulse amplitudewithin a burst of pulses, and the pulse width parameter defining a widthof a pulse within the burst of the pulses.
 14. The method of claim 13,wherein the frequency parameter is about 40 Hz.
 15. The method of claim9, wherein the selecting comprises: temporarily delivering electricalpulses according to the one or more operating parameters to theelectrode adjacent to the central neuronal tissue; and monitoring thepatient's pain while the temporarily delivering is performed.
 16. Themethod of claim 9, wherein the monitoring comprises: determining animprovement in the patient's tinnitus.
 17. The method of claim 9 furthercomprising adjusting stimulation parameters to optimize tinnitus relief.18. A method of treating pure tone tinnitus and noise-like tinnitus in apatient, wherein the patient controls the treatment, the methodcomprising the steps of: selecting one or more operating parameters foran implanted electrical stimulation system that defines burststimulation in combination with tonic stimulation and is effective fortreating the patient's tinnitus; and activating the electricalstimulation system to generate and deliver electrical pulses accordingto the one or more operating parameters to one or more electrodesadjacent to central neuronal tissue.
 19. The method of claim 18, whereinthe selecting comprises: selecting one or more first parameters definingstimulation pulses that are effective in treating a pure tone componentof the patient's tinnitus, the one or more first parameters definingtonic stimulation; and selecting one or more second parameters definingstimulation pulses that are effective in treating a white noisecomponent of the patient's tinnitus, the one or more second parametersdefining burst stimulation.
 20. The method of claim 19 furthercomprising a step of altering one or more operating parameters resultingin optimization of the treatment.
 21. The method of claim 20 furthercomprising a step of storing the altered one or more operatingparameters.
 22. A method of treating a sensory disorder in a patient,comprising: providing first trial stimulation to a patient using tonicstimulation to identify first stimulation parameters for treating atleast a first component of the sensory disorder experienced by thepatient, wherein the first stimulation parameters comprise an electrodecombination and at least one pulse characteristic; providing secondtrial stimulation to a patient using burst stimulation, the second trialstimulation adapted to treat at least a second component of the sensorydisorder that is not fully treated by tonic stimulation; and programmingan implantable pulse generator to generate tonic and burst stimulationpulses according to parameters associated with the first and secondtrial stimulation.
 23. The method of claim 22, wherein the sensorydisorder is chronic pain.
 24. The method of claim 22, wherein thesensory disorder is tinnitus.
 25. A method of treating a sensorydisorder in a patient, comprising: programming an implantable pulsegenerator to define first stimulation parameters for treating at leastone component of a sensory disorder of the patient, the firststimulation parameters defining tonic stimulation; programming theimplantable pulse generator to define second stimulation parameters toprevent or mitigate patient habituation to the tonic stimulation, thesecond stimulation parameters defining burst stimultation; operating theimplantable pulse generator to generate first and second stimulationpulses according to the first and second stimulation parameters; anddelivering the first and second stimulation pulses to neural tissue ofthe patient using one or more electrodes of one or more stimulationleads.
 26. An implantable pulse generator, comprising: pulse generatingcircuitry for generating stimulation pulses; a controller forcontrolling the pulse generating circuitry; and memory for storingoperating parameters defining one or more stimulation programs, whereinthe one or more stimulation programs define stimulation characteristicsfor use by the controller in controlling the pulse generating circuitry,wherein at least one stimulation program includes parameters definingburst stimulation of multiple pulses to occur in succession with aninter-pulse interval of less than 0.005 seconds and tonic stimulation.27. The implantable pulse generator of claim 26, wherein the controllercauses the pulse generating circuitry to generate respective bursts atabout 6, 18, or 40 Hz.